Ran Reshef1, Wael Saber2, Javier Bolaños-Meade3, George Chen4, Yi-Bin Chen5, Vincent T Ho6, Doris M Ponce7, Ryotaro Nakamura8, Michael J Martens9, John A Hansen10,11, John E Levine12. 1. Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY. 2. Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI. 3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. 4. Roswell Park Comprehensive Cancer Center, Buffalo, NY. 5. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. 6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. 7. Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY. 8. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. 9. Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI. 10. Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA. 11. Department of Medicine, University of Washington School of Medicine, Seattle, WA. 12. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract
PURPOSE: Accurate and reproducible methods to diagnose, grade, and report acute graft-versus-host disease (GVHD) are critical for the evaluation of therapies and biomarkers. PATIENTS AND METHODS: The Blood and Marrow Transplant Clinical Trials Network 1202 study is an observational study of 1,709 allogeneic hematopoietic cell transplantation recipients that implemented weekly data reporting and near real-time data adjudication by an end point review committee (ERC), assigning a confidence level (confirmed, probable, possible, or negative) to the diagnosis of acute GVHD at onset. RESULTS: During the first 100 days, symptoms consistent with GVHD developed in 90% of cases but were often determined by centers to be due to causes other than GVHD. Indeed, GVHD was under consideration in only 23% of cases at symptom onset. Diagnostic biopsies were obtained in 40% of cases, but treatment often was incongruous with biopsy findings and 10.5% of biopsies were equivocal. Importantly, more than 40% of steroid courses were started for reasons other than GVHD. The ERC modified the determination of GVHD diagnosis and/or grade in 12.3% of onset cases. The cumulative incidence of acute GVHD as reported by the centers was 62%. When the ERC adjudicated GVHD onset to be present only if the confidence level was probable or confirmed, the incidence of GVHD declined to 49%. CONCLUSION: This study demonstrates that the incidence of GVHD may be overestimated at symptom onset, establishes a contemporary benchmark for acute GVHD, and suggests a structured framework for reporting and adjudication of GVHD that could be used in prospective trials.
PURPOSE: Accurate and reproducible methods to diagnose, grade, and report acute graft-versus-host disease (GVHD) are critical for the evaluation of therapies and biomarkers. PATIENTS AND METHODS: The Blood and Marrow Transplant Clinical Trials Network 1202 study is an observational study of 1,709 allogeneic hematopoietic cell transplantation recipients that implemented weekly data reporting and near real-time data adjudication by an end point review committee (ERC), assigning a confidence level (confirmed, probable, possible, or negative) to the diagnosis of acute GVHD at onset. RESULTS: During the first 100 days, symptoms consistent with GVHD developed in 90% of cases but were often determined by centers to be due to causes other than GVHD. Indeed, GVHD was under consideration in only 23% of cases at symptom onset. Diagnostic biopsies were obtained in 40% of cases, but treatment often was incongruous with biopsy findings and 10.5% of biopsies were equivocal. Importantly, more than 40% of steroid courses were started for reasons other than GVHD. The ERC modified the determination of GVHD diagnosis and/or grade in 12.3% of onset cases. The cumulative incidence of acute GVHD as reported by the centers was 62%. When the ERC adjudicated GVHD onset to be present only if the confidence level was probable or confirmed, the incidence of GVHD declined to 49%. CONCLUSION: This study demonstrates that the incidence of GVHD may be overestimated at symptom onset, establishes a contemporary benchmark for acute GVHD, and suggests a structured framework for reporting and adjudication of GVHD that could be used in prospective trials.
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